The present disclosure is directed to novel taxanes having utility as anti-tumor agents.
The taxane family of terpenes, of which baccatin III and paclitaxel, also commonly referred to as Taxol®, are members, has been the subject of considerable interest in both the biological and chemical arts. Paclitaxel itself is employed as a cancer chemotherapeutic agent and possesses a broad range of tumor-inhibiting activity. Paclitaxel has a 2′R, 3′S configuration and the following structural formula:
wherein Ac is acetyl, Bz is benzoyl, and Ph is phenyl.
Colin et al. reported in U.S. Pat. No. 4,814,470 that certain paclitaxel analogs have an activity significantly greater than that of paclitaxel. One of these analogs, commonly referred to as docetaxel (also known as Taxotere®), has the following structural formula:
wherein Ac is acetyl, Bz is benzoyl, and Ph is phenyl.
Although paclitaxel and docetaxel are useful chemotherapeutic agents, there are limitations to their effectiveness, including limited efficacy against certain types of cancers and toxicity to subjects when administered at various doses. Further, certain tumors have shown resistance to paclitaxel and/or docetaxel. Accordingly, a need remains for additional chemotherapeutic agents with less toxicity and improved efficacy with respect to paclitaxel and/or docetaxel resistant and non-resistant tumors.